Rapid nano-gram scale screening method of micro-arrays to evaluate drug-polymer blends using high-throughput printing technology

Taresco, Vincenzo; Louzao, Iria; Scurr, David J.; Turpin, Eleanor R.; Laughton, Charles A.; Alexander, Cameron; Burley, Jonathan C.; Garnett, Martin

Abstract

A miniaturized, high-throughput assay was optimized to screen polymer-drug solid dispersions using a 2-D Ink-jet printer. By simply printing nanoliter amounts of polymer and drug solutions onto an inert surface, drug:polymer micro-dots of tunable composition were produced in an easily-addressable micro-array format. The amount of material printed for each dried spot ranged from 25 ng to 650 ng. These arrays were used to assess the stability of drug:polymer dispersions with respect to recrystallization, using polarized light microscopy. One array with a panel of 6 drugs formulated at different ratios with Poly (vinylpyrrolidone-vinyl acetate) copolymer (PVPVA) was developed to estimate a possible bulk (gram-scale) approximation threshold from the final printed nano amount of formulation. Another array was printed at a fixed final amount of material to establish a literature comparison of one drug formulated with different commercial polymers for validation. This new approach may offer significant efficiency in pharmaceutical formulation screening, with each experiment in the nano-micro-array format requiring from 3 up to 6 orders of magnitude lower amounts of sample than conventional screening methods.

Citation

Taresco, V., Louzao, I., Scurr, D. J., Turpin, E. R., Laughton, C. A., Alexander, C., …Garnett, M. (in press). Rapid nano-gram scale screening method of micro-arrays to evaluate drug-polymer blends using high-throughput printing technology. Molecular Pharmaceutics, 14(6), https://doi.org/10.1021/acs.molpharmaceut.7b00182

• Journal Article Type: Article
• Acceptance Date: May 14, 2017
• Online Publication Date: May 14, 2017
• Deposit Date: May 17, 2017
• Publicly Available Date: May 17, 2017
• Journal: Molecular Pharmaceutics
• Print ISSN: 1543-8384
• Electronic ISSN: 1543-8392
• Publisher: American Chemical Society
• Peer Reviewed: Peer Reviewed
• Volume: 14
• Issue: 6
• DOI: https://doi.org/10.1021/acs.molpharmaceut.7b00182
• Keywords: High throughput array, Ink-jet printing, Amorphous dispersion, Recrystallisation, Polarizing microscopy
• Public URL: https://nottingham-repository.worktribe.com/output/860398
• Publisher URL: http://pubs.acs.org/doi/abs/10.1021/acs.molpharmaceut.7b00182
• Additional Information: This document is the Accepted Manuscript version of a Published Work that appeared in final form in ACS Medicinal Chemistry Letters copyright © 2017 American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://pubs.acs.org/doi/abs/10.1021/acs.molpharmaceut.7b00182
• Contract Date: May 17, 2017